Rewired glycosylation activity promotes scarless regeneration and functional recovery in spiny mice after complete spinal cord transection

Autor: Joana Nogueira-Rodrigues, Sérgio C. Leite, Rita Pinto-Costa, Sara C. Sousa, Liliana L. Luz, Maria A. Sintra, Raquel Oliveira, Ana C. Monteiro, Gonçalo G. Pinheiro, Marta Vitorino, Joana A. Silva, Sónia Simão, Vitor E. Fernandes, Jan Provazník, Vladimir Benes, Célia D. Cruz, Boris V. Safronov, Ana Magalhães, Celso A. Reis, Jorge Vieira, Cristina P. Vieira, Gustavo Tiscórnia, Inês M. Araújo, Mónica M. Sousa
Rok vydání: 2021
Předmět:
Zdroj: Developmental cell. 57(4)
ISSN: 1878-1551
Popis: Regeneration of adult mammalian central nervous system (CNS) axons is abortive, resulting in inability to recover function after CNS lesion, including spinal cord injury (SCI). Here, we show that the spiny mouse (Acomys) is an exception to other mammals, being capable of spontaneous and fast restoration of function after severe SCI, re-establishing hind limb coordination. Remarkably, Acomys assembles a scarless pro-regenerative tissue at the injury site, providing a unique structural continuity of the initial spinal cord geometry. The Acomys SCI site shows robust axon regeneration of multiple tracts, synapse formation, and electrophysiological signal propagation. Transcriptomic analysis of the spinal cord following transcriptome reconstruction revealed that Acomys rewires glycosylation biosynthetic pathways, culminating in a specific pro-regenerative proteoglycan signature at SCI site. Our work uncovers that a glycosylation switch is critical for axon regeneration after SCI and identifies beta 3gnt7, a crucial enzyme of keratan sulfate biosynthesis, as an enhancer of axon growth. Santa Casa da Misericordia de Lisboa MC-39-2019, Wings for Life WFL-PT-21/20, Portuguese Foundation for Science and Technology UID/BIM/04773/2013/CBMR info:eu-repo/semantics/publishedVersion
Databáze: OpenAIRE